The long-term goal is to provide new methods for statistical analysis of linkage data in gene mapping, thereby increasing reliability and precision of resulting estimates and enhancing the assessment of type I errors in tests for linkage and for heterogeneity. Also, on a long-term basis, the providing of reliable and generally available support for software in linkage analysis. Specific aims are: (1) To develop and implement efficient Monte Carlo methods in human family pedigrees as a prerequisite for computer-based analysis methods; (2) to develop a Monte Carlo method for estimating the p-value (empirical significance level) associated with an observed maximum two-point or multi-point lod score in the very families analyzed by a researcher; (3) to develop methods for finding confidence intervals for parameters such as map distances and to optimize strategies for selecting marker loci for mapping a new locus; (4) to study the effects on gene mapping of unequal marker heterozygosity; (5) to find appropriate p-values in various tests for heterogeneity, particularly in multi-point situations; and (6) to maintain and update computer programs (LIPED, LINKAGE, HOMOG, etc.) for microcomputers and workstations, send copies of programs to researchers requesting them, and keep program users abreast of new developments by circulating a Linkage Newsletter three to four times per year.